Asymmetric benzoxanthene dyes

• Main Authors: KEVIN M. HENNESSEY, JOAN HAUSER, PETER D. THEISEN, STEVEN M MENCHEN, SCOTT C BENSON, VERGINE C. FURNISS
• Format: Patent
• Language: English
• Published: 22.10.1997
• Edition: 6
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAININGELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN,SULFUR, SELENIUM OR TELLURIUM; ADHESIVES; BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS OR TEST PAPERS THEREFOR; COMPOSITIONS THEREOF; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL ORENZYMOLOGICAL PROCESSES; CULTURE MEDIA; DERIVATIVES THEREOF; DYES; ENZYMOLOGY; HETEROCYCLIC COMPOUNDS; INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIRCHEMICAL OR PHYSICAL PROPERTIES; LAKES; MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FORELSEWHERE; MEASURING; MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEICACIDS OR MICROORGANISMS; METALLURGY; MICROBIOLOGY; MICROORGANISMS OR ENZYMES; MISCELLANEOUS APPLICATIONS OF MATERIALS; MISCELLANEOUS COMPOSITIONS; MORDANTS; MUTATION OR GENETIC ENGINEERING; NATURAL RESINS; NUCLEIC ACIDS; NUCLEOSIDES; NUCLEOTIDES; ORGANIC CHEMISTRY; ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES; PAINTS; PHYSICS; POLISHES; PROCESSES OF PREPARING SUCH COMPOSITIONS; PROPAGATING, PRESERVING OR MAINTAINING MICROORGANISMS; SPIRITS; SUGARS; TESTING; VINEGAR; WINE

A class of asymmetric monobenzoxanthene compounds useful as fluorescent dyes are disclosed having the structure wherein Y1 and Y2 are individually hydroxyl, amino, imminium, or oxygen, R1-R8 are hydrogen, fluorine, chlorine, alkyl, alkene, alkyne, sulfonate, amino, amido, nitrile, alkoxy, linking group, and combinations thereof, and R9 is acetylene, alkane, alkene, cyano, substituted phenyl, and combinations thereof. The invention further includes novel intermediate compounds useful for the synthesis of asymmetric benzoxanthene compounds having the general structure where substituents R3-R7 correspond to like-referenced substituents in the structure of described above, and Y2 is hydroxyl or amine. In another aspect, the invention includes methods for synthesizing the above dye compounds and intermediates. In yet another aspect, the present invention includes reagents labeled with the asymmetric benzoxanthene dye compounds, including deoxynucleotides, dideoxynucleotides, phosphoramidites, and polynucleotides. In an additional aspect, the invention includes methods utilizing such dye compounds and reagents including dideoxy polynucleotide sequencing and fragment analysis methods.